Narazaciclib  (Synonyms: ON123300)

Narazaciclib (ON123300), a strong and brain-penetrant^[1] multi-kinase inhibitor, inhibits CDK4 (IC₅₀=3.9 nM), Ark5 (IC₅₀=5 nM), PDGFRβ (IC₅₀=26 nM), FGFR1 (IC₅₀=26 nM), RET (IC₅₀=9.2 nM), and FYN (IC₅₀=11 nM). Single agent Narazaciclib causes a dose-dependent suppression of phosphorylation of Akt as well as activation of Erk in brain tumors^[2]. Narazaciclib inhibits CDK6 with an IC₅₀ of 9.82 nM^[3].

Narazaciclib (ON123300) inhibits U87 glioma cell proliferation with an IC₅₀ of 3.4±0.1 μM^[2]. Narazaciclib (1 and 10 μM) inhibits cell proliferation in a panel of 11 glioma models including a patient-derived model (GBM10)^[2].
Narazaciclib (6.3 μM; 1 h) reduces phosphorylation of Akt and its downstream signaling components, P70S6K, 40S rpS6 and Rb S780, yet ON123300 induces Erk activation in U87 cells; both in a dose- and time-dependent manner^[2]. ON123300 inhibits PI3Kδ with the IC₅₀ of 144nM^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Narazaciclib (ON123300) decreases p-Akt expression and increases p-Erk activity in brain tumors upon administration at both IV doses of 5 mg/kg and 25 mg/kg in U87 brain tumor-bearing mouse. The half-life (T_1/2) is 1.5 h for 5 mg/kg and 25 mg/kg in plasma^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

429.52

C₂₄H₂₇N₇O

1357470-29-1

Solid

Yellow to orange

N#CC1=CC2=CN=C(NC3=CC=C(N4CCN(C)CC4)C=C3)N=C2N(C5CCCC5)C1=O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Hua Lv, et al. Integrated pharmacokinetic-driven approach to screen candidate anticancer drugs for brain tumor chemotherapy. AAPS J. 2013 Jan;15(1):250-7.  [Content Brief]

  [2]. Xiaoping Zhang, et al. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol Cancer Ther. 2014 May;13(5):1105-16.  [Content Brief]

  [3]. S K A Divakar, et al. Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas. Leukemia. 2016 Jan;30(1):86-93.  [Content Brief]